During gestation, the immunological reactivity of a female is often changed in the direction of "tolerance". This maternal immunologic unresponsiveness is demonstrable with transplanted allogeneic tissues, and is specific in that it depends upon a genetic concordance between the conceptus and the subsequent tissue transplant. In nature, this phenomenon may serve to protect the fetus from the consequences of maternal isoimmunization. We are investigating the nature and mechanisms of this tolerance induction. We postulate that this information might be applied to various clinical problems, e.g., cancer in general, choriocarcinoma, certain diseases of pregnancy, and the transplantation of tissues and organs. We have shown that in the absence of maternal unresponsiveness a pecentage of conceptuses are apparently vulnerable and succumb to allograft rejection. This result was obtained by preimmunization of prospective mothers with neoplastic rather than normal tissues, and this observation suggests cross reacting immunogenicity common to both fetal and neoplastic tissues. This possibility is being further explored.